Ontology highlight
ABSTRACT:
PROVIDER: PRJNA349068 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4436190_1.fastq.gz | Fastqsanger.gz | |||
| SRR4436190_2.fastq.gz | Fastqsanger.gz | |||
| SRR4436200_1.fastq.gz | Fastqsanger.gz | |||
| SRR4436200_2.fastq.gz | Fastqsanger.gz | |||
| SRR4436210_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 208 |
Similar Datasets
Project description:Human eggs were fertilized with sperm carrying a homozygous mutation in the EYS gene at rs758109813 and treated with a Cas9 RNP targeting this mutation at either fertilization or at the 2-cell stage. The purpose of this analysis was to determine loss of heterozygosity due to CRISPR-induced chromosomal changes. We find that However, in half of the embryos, the break remains unrepaired throughout the first cell cycle, resulting in both segmental, as well as whole chromosome loss. These embryos appear as corrected non-mosaic wild type embryos in an on-target sequence analysis, but are not viable. These results show a surprising tolerance of the human embryo for mitotic entry with unrepaired DNA double strand breaks, and suggest that pericentromeric cleavage by Cas9 may enable the allele-specific removal of chromosomes in trisomic embryos.
2020-10-29 | GSE148488 | GEO
Project description:Mitochondrial DNA (mtDNA) quantitative and qualitative defects have been associated with impaired human embryonic development, but the underlying mechanisms remain unknown. By using human embryos affected by mitochondrial disorders as models of mitochondrial dysfunction, we compared gene expression between 9 mitochondrial embryos (carriers of a pathogenic variant in a mtDNA or a nuclear gene coding for a mitochondrial protein) to 33 controls. Transcriptomic analyses performed by RNA-Sequencing revealed a similar global transcriptional repression in mitochondrial embryos affecting a significant proportion of differentiation factors and nuclear genes encoding mitochondrial proteins. If oxidative phosphorylation was at the top of the most significant deregulated pathways, cell survival and autophagy were found to be significantly decreased in these embryos, questioning their viability. Differentially expressed genes identified in this study represent good predictive biomarkers of mitochondrial dysfunction and should be tested as markers of preimplantation development.
2023-02-27 | E-MTAB-11531 | biostudies-arrayexpress
Project description:To study whether increase in mitochondrial oxidative stress (SOD2 removal) and decrease in mitochondrial DNA repair (Ogg1 dMTS) results into increase in mitochondrial DNA mutation load. Oxidative stress has been suggested to induce mutations in mtDNA. To verify this, we extracted and sequenced (Illumina) mitochondrial DNA from heart Sod2 knockout animals that were also deficient for mitochondrial base-excision repair. The repair deficiency was induced by removing the genomic region encoding for the predicted mitochondrial targeting sequence from endogenous OGG1 (L2 to W23) called Ogg1 dMTS mice, thus excluding the protein from mitochondria. OGG1 is a DNA glycosylase that recognizes and repairs 8-oxo-dG damage from DNA. Oxidative stress can induce 8-oxo-dG lesions, thus we removed the mitochondrial matrix localized superoxide dismutase (SOD2) from these mice to increase the level of oxidative stress. 8-oxo-dG lesion can be mutagenic because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.
2018-07-13 | E-MTAB-6533 | biostudies-arrayexpress
Project description:We investigate the participation of miRNAs in the cell response to the mitochondrial dysfunction associated with m.3243A>G mutation in mitochondrial DNA (mtDNA), which is the most common cause of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome.Through small-RNA sequencing and in silico analysis, we identified 246 differentially-expressed in a transmitochondrial cybrid model of MELAS (100% m.3243A>G mutant mitochondrial DNA), with 126 being up-regulated and 120 down-regulated. The enrichment analysis of Gene Ontology (GO) terms revealed that target genes for dysregulated miRNAs were involved in muscle and nervous system development, heart development, and signaling pathways controlling cardiac events.These data suggest that the miRNA program triggered by the MELAS m.3243A>G mutation could explain for some of the clinical manifestations of the MELAS syndrome.
2019-03-29 | GSE113300 | GEO
Project description:Studying whether removal of base-excision repair from mitochondria will result into increase in mitochondrial DNA (mtDNA) mutation load. The endogenous genes of OGG1 and MUTYH DNA glycosylases were modified to lack the genomic region encoding for the predicted mitochondrial targeting sequence. The mouse lines used: A mouse line that lacks the region encoding for the mitochondrial targeting sequence (L2 to W23) of OGG1 (Ogg1 dMTS mice). A mouse line that lacks the region encoding the mitochondrial targeting sequence (K2 to P33) of MUTYH (Mutyh dMTS mice). To accumulate mutations to the mitochondrial DNA these mice were bred double homozygous Mutyh dMTS x Ogg1 dMTS mice as a maternal lineage for five consecutive generations and mitochondrial DNA from liver was extracted from the offspring and sequenced with Illumina. OGG1 and MUTYH are involved in repair of 8-oxo-dG from DNA. 8-oxo-dG can be a mutagenic lesion because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.
2018-07-13 | E-MTAB-6532 | biostudies-arrayexpress
Project description:It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction, including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B 0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction. time series
2011-11-22 | E-GEOD-33831 | biostudies-arrayexpress
Project description:Environmental factors, including diet, can influence gene expression and developmental outcomes through epigenetic modifications. While maternal diet is known to affect offspring DNA methylation and phenotypes, its impact on the oocyte and subsequent embryo epigenome remains less understood. Here, we investigated how maternal methionine supplementation affects DNA methylation patterns in oocytes and embryos of Polypay ewes. Whole genome bisulfite sequencing (WGBS) was performed on oocytes collected from 16 twin ewe pairs (8 methionine-treated and 8 control). These ewes were later bred to control rams, and embryos were flushed for WGBS as well. In oocytes, 2,056 differentially methylated cytosines (DMCs) were identified, with 2,034 hypomethylated and 22 hypermethylated. Additionally, 17 mitochondrial DMCs were identified, with 12 hypermethylated and 5 hypomethylated. In embryos, 113 DMCs were identified, with 112 hypermethylated and only one hypomethylated. Mitochondrial DNA analysis revealed 22 hypermethylated DMCs. To assess the inheritance of methyl marks, we compared DMCs between oocytes and embryos. While no direct overlaps were found in nuclear DNA, three CpGs exhibited opposite methylation trends—hypomethylated in oocytes but hypermethylated in embryos. In contrast, five mitochondrial DMCs overlapped between oocytes and embryos. To functionally assess the role of differentially methylated genes, we performed siRNA-mediated knockdown of two embryo DMC-associated genes: SCRIB and CERS3. Knockdown of SCRIB led to a 16.4% average decrease in blastocyst formation rate (p = 0.001), while CERS3 knockdown resulted in a 9.5% decrease (p = 0.005). These results demonstrate that maternal methionine supplementation alters both nuclear and mitochondrial DNA methylation in oocytes and embryos and that affected genes may play critical roles in early embryonic
2025-11-18 | GSE304764 | GEO